There is a continuing need in the art to develop new ways of treating and/or preventing infection by pathogens. Broadly speaking, vaccines in the art are based on inactivated or attenuated infectious agents or synthetic antigens that are administered to patients in a primary immunization followed by a secondary booster immunization normally given to a patient several weeks after the primary inoculation in order to provide the necessary protective immunity in the patient. While adjuvants are often included in vaccine compositions to enhance the immune response, comparatively few adjuvants have been approved for use in vaccines administered to humans. There is a particular need for safe adjuvants that can be delivered by the nasal route or by inhalation. Nasal vaccines have a particular usefulness because they can be self-administered and does not require a clinician. This is advantageous in mass vaccination programs or in the developing countries where there is a shortage of trained personnel.
Studies by Shibata et al. (1-4) have shown that oral delivery of 1-10 μm phagocytosable chitin particles results in an elevation of Th1 cytokines in mouse spleen cell cultures. The effect was specific to particulates as no elevation was produced by soluble chitin. It could also be reproduced using 1 μm polystyrene microspheres coated with N-Acetyl-D-Glucosamine, which is the main component of chitin. It was also demonstrated that oral administration of chitin down-regulates serum immunoglobulin E (IgE) and lung eosinophilia in a murine model of ragweed allergy (1).
Shibata et al. have also developed a mouse model of allergic airway inflammation and orally administered chitin preparations to the mice (1). Ragweed-specific IgE levels were significantly reduced after daily oral administration of chitin to ragweed-sensitized mice, before and during immunization. Bronchioalveolar lavage (BAL) cells were harvested 14 days after immunization and a reduction in the levels of eosinophil and lymphocyte levels was observed after chitin treatment. Lung inflammation was determined histologically 14 days after immunization, and peribronchial, perivascular, and total lung inflammation were inhibited in the chitin-treated group.
When chitin was administered prophylactically to mice who were subsequently administered ragweed, IL-4, IL-5, and IL-10 production was significantly reduced and low, although significant levels of IFN-γ were detected. Chitin also has a prophylactic effect when administered to C57BL6 mice, which are considered higher responders for cell-mediated immunity/Th1 responses, but lower responders for allergic responses, compared with BALB/c mice. When ragweed-sensitized mice were treated simultaneously with ragweed and chitin, the resulting levels of IL-4, IL-5, and IL-10 were significantly reduced compared to those stimulated by ragweed alone.
However, while Shibata et al. disclose the use of chitin microparticles for the treatment of allergy, the compositions are administered orally as a supplement to activate macrophages and prophylactically strengthen the immune system in the absence of recurrent bacterial infections that are decreasingly common in industrialized countries.
Japanese Patent Application No. 19997-0087986 A (Unitika Limited) discloses the use of deacetylated chitin particles (e.g., chitosan compositions) in the form of powders, granules, or fibres for delivery to the nasal mucosa. The chitosan particles have an effective particle diameter of 20 to 250 microns and are proposed for the treatment of allergic symptoms at an inflammatory site such as pollinosis.
U.S. Pat. No. 5,591,441 9 (Medical Sciences Research Institute) concerns the use of particulate compositions for providing protection against microorganism infection and biological warfare agents. The compositions are delivered intravenously with the aim of providing a short lived increased in in vivo peroxide levels to kill the microorganisms.
In our earlier patent application WO 03/015744, we describe the use of chitin microparticle preparations (CMP) for the treatment of allergy, conditions benefiting from an up-regulation of the cell mediated immune system, such as bacterial infection, fungal infection, and viral infection, and conditions that would benefit from an up-regulation of natural killer (NK) cell activity and/or the secretion of interferon-γ (IFN-γ), such as the treatment of cancer.
Danbiosyst has filed patent applications in which chitosan, a deacetylated form of chitin, is used as a drug delivery system, in particular for targeting the mucosa of patients. WO 98/30207 relates to the use of chitosan for transporting active agents across mucosa using compositions comprising chitosan, type A cationic gelatin, and a therapeutic agent. WO 97/20576 relates to the use of chitosan as an adjuvant for intranasal administration with an antigen with the aim of improving the antigenicity of the antigen when the composition is used to immunize a subject. WO 90/09780 discloses the use of microcapsules containing chitosan for drug delivery across mucosa. Chitosan is described in these applications as being produced from chitin by a hydrolysis reaction in which the greater proportion of the N-acetyl groups in chitin are removed, typically providing levels of deacetylation of about 90%.
There are many examples in the art where there are opportunities for improving the protection afforded to individuals through the development or improvement of vaccine compositions. The following are examples wherein there is a need for more effective protection.
Pseudomonas aeruginosa, an opportunistic pathogen, is a leading cause of life threatening infections in immunocompromised individuals and is a major risk to patients on ventilator support and/or suffering from many disease conditions in which there is a reduction in lung function and a reduced ability to clear infections. Each year, over two million patients die as a result. A report on the incidence of hospital-associated infections places P. aeruginosa among the three most frequently reported pathogens (5). P. aeruginosa is also a common cause of chronic and life threatening pulmonary infection in cystic fibrosis patients. Recent reports list P. aeruginosa among the most serious antibiotic-resistant bacteria and one for which effective vaccines are needed (6).
Streptococcus pneumoniae is a ubiquitous pathogen and responsible for a high proportion of cases of pneumonia (both lobar and bronchopneumonia). It is one of the leading causes of illness and death among young children, the elderly and those with an impaired immune system as the result of diseases such as AIDS, or immunosuppressive therapy such as for bone marrow transplantation. The invasive form of Streptococcal infection, in which the bacteria disseminate into the blood and other organs leads to very serious complications. Each year in the United States, pneumococcal disease is estimated to cause 3000 cases of meningitis, 50,000 cases of bacteraemia, 125,000 hospitalizations and 6,000,000 cases of Otitis media. There is also a growing concern about the emergence of antibiotic resistant strains of S. pneumoniae. 
Recently, risk of influenza pandemics, for example arising from avian influenza, has raised awareness of the need for effective prevention and treatment of infection in the population.
Furthermore, in the Third World, the population is exposed to many infectious agents and infection might be prevented or ameliorated by the development of effective and economic vaccines. Examples of conditions that might be treatable include malaria. Malaria, a parasitic infection, is an important cause of mortality and morbidity in many parts of the world. It affects 300-500 million people and kills 1-2 million each year, mostly children under the age of 5 years. Malaria has a devastating effect on economic development in the Third World. The recent appearance of drug-resistant strains is causing great concern and the changes in global climate are presenting an elevated incidence in developed countries as well.
It would be a considerable advantage in these countries to have available vaccines that are capable of providing protection after a course of administration over a short period of time to help to avoid the need for a secondary booster inoculation several weeks after the primary inoculation.